Individuals with cystic fibrosis (CF) are commonly colonized with Pseudomonas aeruginosa. The chronic infections caused by P. aeruginosa are punctuated by acute exacerbations of the lung disease, which lead to significant morbidity and mortality. As regulators of virulence determinants, P. aeruginosa quorum-sensing systems may be active in the chronic lung infections associated with CF. We have examined the levels of autoinducer molecules and transcript accumulation from the bacterial populations found in the lungs of patients with CF. We detected biologically active levels of N-(3-oxododecanoyl)-L-homoserine (3-oxo-C12-HSL) and N-butyryl-L-homoserine lactone (C4-HSL) in sputum from CF patients. Interestingly, it appears that C4-HSL is less frequently detected than 3-oxo-C12-HSL in the lungs of patients with CF. We also examined the transcription of the autoinducer synthase gene lasI and showed that it is frequently expressed in the lungs of patients with CF. We observed a significant correlation between the expression of lasI and four target genes of the Las quorum-sensing system. Taken together, our results indicate that quorum-sensing systems are active and may control virulence factor expression in the lungs of patients with CF.Quorum-sensing signaling systems allow bacteria to regulate gene expression in a population-dependent manner. Quorumsensing regulatory mechanisms are widespread; they have been described in numerous gram-positive (18) as well as gramnegative (9, 42) bacteria. In acyl-homoserine lactone-based systems, growing bacteria produce small signaling molecules (autoinducers) that accumulate in the surrounding environment. At a specific cell density, the concentration of autoinducer becomes sufficient to interact with the autoinducer-dependent transcriptional activator protein and alter gene expression.In Pseudomonas aeruginosa, quorum-sensing systems have been extensively studied. Two acyl-homoserine lactone-based systems, the las (10) and rhl (25) systems, have been described. These operate in a hierarchical fashion along with a recently described quinolone signaling system (33) to regulate as much as 4% of the genome (45). LasI and RhlI synthesize the autoinducers N-(3-oxododecanoyl)-L-homoserine lactone (3-oxo-C12-HSL) (29) and N-butyryl-L-homoserine lactone (C4-HSL) (30), respectively. LasR and RhlR bind DNA to modify transcription of target genes only after a threshold level of their respective autoinducers is reached.Quorum-sensing systems are believed to be central to the pathogenesis of P. aeruginosa (reviewed by Rumbaugh et al. [34]). One such infection in which quorum sensing may play an important role is the P. aeruginosa lung infections associated with cystic fibrosis (CF). These infections may be the perfect environment for the expression of the quorum-sensing systems, as the lungs are a spatially limited environment and P. aeruginosa can grow to high densities (10 7 to 10 8 /ml) (40) in sputum. These conditions should be sufficient to induce expression of P. aeruginosa quorum-sens...

A breakdown in intestinal barrier function and increased bacterial translocation are key events in the pathogenesis of sepsis and liver disease. Altering gut microflora with noninvasive and immunomodulatory probiotic organisms has been proposed as an adjunctive therapy to reduce the level of bacterial translocation and prevent the onset of sepsis. The purpose of this study was to determine the efficacy of a probiotic compound in attenuating hepatic and intestinal injury in a mouse model of sepsis. Wild-type and interleukin-10 (IL-10) gene-deficient 129 Sv/Ev mice were fed the probiotic compound VSL#3 for 7 days. To induce sepsis, the mice were injected with lipopolysaccharide (LPS) and D-galactosamine (GalN) in the presence and absence of the peroxisome proliferator-activated receptor gamma (PPAR␥) inhibitor GW9662. The mice were killed after 6 hours, and their colons were removed for the measurement of the cytokine production and epithelial function. The functional permeability was assessed by the mannitol movement and cyclic adenosine monophosphate-dependent chloride secretion in tissue mounted in Ussing chambers. The livers were analyzed for bacterial translocation, cytokine production, histological injury, and PPAR␥ levels. The tissue levels of tumor necrosis factor alpha, interferon gamma, IL-6, and IL-12p35 ribonucleic acid were measured by semiquantitative reverse transcription polymerase chain reaction. L iver dysfunction and failure contribute to the high mortality rates seen in patients with Gram-negative sepsis. The presence of lipopolysaccharide (LPS) from Gram-negative bacteria in the systemic circulation results in the activation of the innate immune system and the secretion of high levels of proinflammatory cytokines. In animal models, LPS challenge can induce a systemic reaction resulting in a sepsis-like condition characterized by fever, hypotension, and widespread tissue damage. D-Galactosamine (GalN) increases the susceptibility of mice to LPS-induced shock by impairing liver metabolism. 1 Challenging mice with low doses of LPS in conjunction with GalN results in massive liver apoptosis and increased mortality.Tumor necrosis factor alpha (TNF-␣) plays a central role in the overwhelming systemic inflammatory response to LPS. 2 However, the complete blockade of TNF-␣ production does not improve survival in animals or humans 3 The activation of nuclear factor kappa B (NF-B) has been shown to play a key role in the pathogenesis of sepsis and is a pivotal step in the regulation of several immune and proinflammatory genes, including TNF-␣. 4 The modulation of NF-B activity has been proposed as a strategy for reducing the mortality associated with sepsis. Peroxisome proliferator-activated receptor gamma (PPAR␥) is a nuclear hormone receptor and transcription

Background By targeting the distal branches of the femoral nerve in the mid-thigh, the adductor canal block (ACB) can preserve quadriceps muscle strength while providing analgesia similar to a conventional femoral nerve block (FNB) for inpatients undergoing major knee surgery. In this randomized, double-blind, noninferiority trial, the authors hypothesized that ACB provides postoperative analgesia that is at least as good as FNB while preserving quadriceps strength after outpatient anterior cruciate ligament reconstruction. Methods A total of 100 patients were randomized to receive ACB or FNB with 20 ml ropivacaine 0.5% (with epinephrine). The authors sequentially tested the joint hypothesis that ACB is noninferior to FNB for cumulative oral morphine equivalent consumption and area under the curve for pain scores during the first 24 h postoperatively and also superior to FNB for postblock quadriceps maximal voluntary isometric contraction. Results The authors analyzed 52 and 48 patients who received ACB and FNB, respectively. Compared with preset noninferiority margins, the ACB–FNB difference (95% CI) in morphine consumption and area under the curve for pain scores were −4.8 mg (−12.3 to 2.7) (P = 0.03) and −71 mm h (−148 to 6) (P < 0.00001), respectively, indicating noninferiority of ACB for both outcomes. The maximal voluntary isometric contraction for ACB and FNB at 45 min were 26.6 pound-force (24.7–28.6) and 10.6 pound-force (8.3–13.0) (P < 0.00001), respectively, indicating superiority of ACB. Conclusion Compared with FNB, the study findings suggest that ACB preserves quadriceps strength and provides noninferior postoperative analgesia for outpatients undergoing anterior cruciate ligament reconstruction.

Ultrasound assessment of gastric volume by clinical anesthesiologists is highly reproducible with high intrarater and interrater reliability. The free-tracing method to measure antral cross-sectional area is equivalent to the two-diameter method.

Bilateral TAP blocks do not provide additional analgesic benefit when added to trocar insertion site local anesthetic infiltration and systemic analgesia for laparoscopic gastric-bypass surgery.

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